We are developing better ophthalmic drug delivery vehicles.
We have developed novel nanoparticle-laden soft contact lenses
that deliver ophthalmic drugs for a period of about 5-6 days
with significantly smaller drug loss to the systemic circulation.
Animal trials of these lenses are planned and a product based
on this technology is expected to be in the market in about
8 years. We are also interested modeling the process of nanoparticle
encapsulation in the gels as well as the drug release from
the particles, subsequent diffusion processes. Our work in
this area has received much recent attention in the popular
press including, CNN Headline News, and was listed in Reader's
Digest Medical Breakthroughs 2004.

Ophthalmic
Drug Delivery by Particle Laden Contact Lenses
Only about 1-5% of drugs delivered via eye drops reach
cornea and the rest enters systemic circulations and
causes side effects. We have developed transparent
particle-laden contact lenses that deliver drugs at
therapeutic doses for 5-30 days and that can lead
to a 40 fold increase in the fraction of the entrapped
drug that enters the cornea.

Our group is combining mathematical modeling with In vitro
experiments to develop an understanding of various physiological
processes in the eyes and to understand factors that contribute
to ‘dry eyes’, which is the most common ocular
ailment, and also to develop possible treatments and efficient
drug delivery vehicles. We have developed a model for tear
dynamics that can predict the steady state tear film thickness,
salt concentration and the electrical potential in the eye,
and the dependency of these on physiological parameters such
as tear secretion rates, salt concentration in the secreted
tears, elastic properties of canaliculi, tear evaporation
rates, etc. This model helps us understand various aspects
of tear film dynamics and also helps us identify potential
dry eye treatments. We are also studying a number of transport
issues of relevance in ophthalmology. These include lipid
spreading on the surface of the tear film, tear film breakup
and transport of drug from the front surface of the eye to
the retina. The eventual goal of our research efforts is to
combine experiments and modeling to develop a comprehensive
quantitative model for transport in the eye.

Drug overdose is a major health care problem, as a number
of widely used drugs can cause life-threatening toxicities
and are without antidotes. Amitriptyline is one of the most
widely prescribed tricyclic antidepressant in the United States,
and it is also a common vehicle for suicide. Since no specific
antidotes exist for this drug, the only method of overdose
treatment is sequestration of the drug to reduce the free
drug concentration. We are exploring the feasibility of using
liposomes that can potentially sequester amitriptyline from
blood for overdose treatment. We have developed various liposomal
systems, both pegylated and unpegylated, that bind a significant
amount of amitriptyline due to electrostatic interactions,
and these reduce the free drug concentrations in human serum
by more than 80%.

Schematic showing
an IV injection of liposomes (green circles) into
the circulatory system (top). The bottom schematic
shows a magnified view of a tissue with liposomes
flowing through the capillaries and adsorbing the
flowing drug (purple circles) leading to reduction
in free drug concentration.

Drug
Overdose Treatment by Liposomes
About 300,000 patients visit emergency room each year
due to drug toxicity. Currently, there are no antidotes
to treat certain types of drug overdoses. We aim to
develop liposomes that can be injected intravenously
to sequester drugs and treat overdoses.

In human serum about 92% of the drug (amitriptyline)
is bound to proteins (blue circles). Addition of DMPC:DOPG
liposomes (pegylated, orange squares or unpegylated,
triangles) increases the bound fraction to 96%-98%
leading to at least 50% reduction in free concentration.

Our group is also interested in the area of bioseparations,
where we use microfluidic devices for DNA amplification
and protein separation; in the area of interfacial and colloidal
phenomena, where we focus on the transport of fluids across
surfactanct-covered monolayers.